Pathobiology and Reversibility of Prediabetes in a Biracial Cohort

描述（由申请人提供）：一项双种族队列（PROP-ABC）研究拟研究一个现存队列，包括约400名血糖正常的非裔美国人和2型糖尿病父母的白种人后代，再进行5年的研究。这些研究对象在2006年至2009年期间入组，并一直随访到2012年，在此期间，有11人患有糖尿病，100人患有前驱糖尿病，没有证据表明存在种族差异。本研究的目的是通过评估种族在血糖进展第二波中的作用，以及前驱糖尿病可逆性的时间依赖性，更全面地了解早期血糖异常的自然史和代谢预测因子。该研究检验了4个假设：1)在父母患有2型糖尿病的后代中，从正常到血糖调节受损的早期进展（5年内）发生在最高风险受试者中，与种族无关，而晚期进展（5-10年）显示种族差异，并由生理、生化和行为标志物预测；2)早期微血管并发症、外周血管疾病（PVD）和内皮功能障碍在血糖调节从正常到受损的转变过程中表现出来，存在种族差异，并由血糖和非血糖因素预测；3)在非裔美国人和2型糖尿病父母的白种人后代中，“代谢健康”胰岛素敏感型肥胖（ISO）表型与心脏代谢危险因素和发生血糖异常的关系存在种族差异；4)糖尿病前期状态的持续时间是生活方式疗效的主要决定因素，并与之呈负相关

DESCRIPTION (provided by applicant): The Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study proposes to study an extant cohort, comprising ~400 normoglycemic African American and Caucasian offspring of parents with type 2 diabetes for an additional 5-year. The subjects were enrolled between 2006 and 2009 and have been followed up to 2012, during which 11 have developed diabetes and 100 developed prediabetes, without evidence of racial disparities. The objective of the present proposal is to gain a fuller understanding of the natural history and metabolic predictors of early glucose abnormalities, by assessing the role of race during the second wave of glycemic progression, and the time dependency of reversibility of prediabetes. The study tests 4 hypotheses: 1) Among offspring of parents with type 2 diabetes, early progression from normal to impaired glucose regulation (within 5 yr.) occurs in the highest-risk subjects independently of race, whereas late progression (5-10 yr.) displays racial disparities, and is predicted by physiological, biochemical and behavioral markers; 2) Early microvascular complications, peripheral vascular disease (PVD), and endothelial dysfunction manifest during transition from normal to impaired glucose regulation, display racial disparities, and are predicted by glycemic and nonglycemic factors; 3) The "metabolically healthy" insulin-sensitive obese (ISO) phenotype displays racial disparities in its association with cardiometabolic risk factors and incident dysglycemia among African-Americans and Caucasians offspring of parents with type 2 diabetes; and 4) Duration of the prediabetic state is a major determinant of, and is inversely related to, the efficacy of lifestyle intervention to induce regression of the prediabetic phenotype and restoration of normal glucose regulation. The 100 participants with prediabetes will receive Intensive Lifestyle intervention (ILI), to reverse prediabetes and restore normoglycemia. The ~260 participants who have maintained normal glucose status will continue follow-up for 5 years; persons who develop prediabetes will immediately receive ILI. Understanding the predictors of the escape from normoglycemia, the role of race, and the reversibility of new-onset prediabetes is of utmost importance, because the discovery of interventions for reversal of prediabetes will also help eliminate ethnic disparities in downstream diabetes events. The additional 5 years of follow-up will provide data on 10-yr rates and predictors of incident prediabetes, racial patterns during the second wave of progression, and, time-dependent reversibility of prediabetes. Focusing on prediabetes is of immense public health significance, as its successful reversal prevents diabetes and associated complications.